Comparison of a 250 kV single-stage accelerator mass spectrometer with a 5 MV tandem accelerator mass spectrometer--fitness for purpose in bioanalysis.

The introduction of 'compact' accelerator mass spectrometers into biomedical science, including use in drug metabolism and bioanalytical applications, is an exciting recent development. Comparisons are presented here between a more established and relatively large tandem accelerator which operates at up to 5 MV and a conventional laboratory-sized 250 kV single-stage accelerator mass spectrometer. Biological samples were enriched with low levels of radiocarbon, then converted into graphite prior to analysis on each of the two instruments. The data obtained showed the single-stage instrument to be capable of delivering comparable results, and thus able to provide similar study support, with that provided by the 5 MV instrument, without the significant overheads and complexities which are inherent to the operation of the larger instrument. We believe that the advent of these laboratory-sized accelerator mass spectrometry (AMS) instruments represents a real turning point in the potential for application of AMS by a wider user group.

Determination of salmeterol in rat and dog plasma by high-performance liquid chromatography with fluorescence detection.

Salmeterol (as the hydroxynaphthoate) is the first of a new class of long-acting beta-adrenergic receptor agonists with both bronchodilator and anti-inflammatory actions. A sensitive, accurate, and precise high-performance liquid chromatographic method for the determination of salmeterol in rat and dog plasma is described. Samples are prepared by solid-phase extraction and, after chromatography of the extracts on a reversed-phase styrene/divinylbenzene analytical column, salmeterol is detected by fluorescence monitoring (excitation wavelength, 230 nm; emission wavelength, 305 nm). The method is sensitive to 1 ng/mL, at which concentration the coefficient of variation was 16.3% in a single assay run. Repeated analyses of quality control samples, nominally at 2 ng/mL, were carried out over a number of assay runs with a coefficient of variation of 10.4%. The method is specific for salmeterol with respect to endogenous plasma components and identified metabolites. The assay was applied to the analysis of salmeterol in plasma of rats and dogs from pharmacokinetic studies.

Determination of ondansetron in plasma and its pharmacokinetics in the young and elderly.

Ondansetron is a 5-hydroxytryptamine3 receptor antagonist for the treatment of chemotherapy- and radiotherapy-induced nausea and emesis. A sensitive, accurate, and precise HPLC method for the determination of ondansetron in plasma is described. Samples are prepared by solid-phase extraction and, after chromatography of the extracts on a silica analytical column, ondansetron is detected by UV absorbance at 305 nm. The method is sensitive down to 1 ng/mL, at which concentration the coefficient of variation was 6.2% in a single assay run. Repeated analyses of quality control samples, nominally at 2 ng/mL, were carried out over a number of assay runs with a coefficient of variation of 5.5%. The method is specific for ondansetron with respect to endogenous plasma components, identified phase I metabolites, and some co-administered chemotherapeutic drugs. In sustained use over several months, and in support of the clinical development of ondansetron, the method has been shown to be robust. An application of the assay in the investigation of the pharmacokinetics of ondansetron in the young and elderly is described.